We have defined some of the effects of oxygen radicals (superoxide, hydoxyl, and hydrogen peroxide) in inflammation, by using several in vitro models of inflammatory cellular interactions. We have examined the conditions which cause macrophages to become activated to produce oxygen radicals. We have shown that scavengers of oxygen radicals and other agents which protect responding lymphocytes from damage by oxygen radicals enhance both proliferative and differentiative functions of murine lymphocytes, in vitro. Similarly, agents which stimulate oxygen radical production by macrophages cause suppression of lymphocyte functions unless additional protective mechanisms are supplied. We have shown that agents present in chronic inflammation (bacterial endotoxin, cytokines) activate macrophages to release oxygen radicals. We have demonstrated an intimate relationship between the production of oxygen radicals and prostaglandins. In studies of patients with either Hodgkin's disease or chronic periodontitis, we have shown the presence of macrophages which produce oxygen radicals and prostaglandins, thereby suppressing lymphocyte responses. Definition of the role of oxygen radicals in chronic inflammation can lead to modulation of both the tissue destruction and immune response.